- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04474626
Isoquercetin in Sickle Cell Anemia
Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease
This research study is being done to assess the safety and effectiveness of isoquercetin to reduce levels of soluble P-Selectin in patients with sickle cell disease. Isoquercetin is a naturally occurring flavonoid-or vitamin. You will find quercetin and isoquercetin in fruits and vegetables.
The names of the study drug involved in this study are/is:
- Isoquercetin
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a single-arm phase 2 study in adults with Sickle Cell Disease (SCD) to assess the effect of oral isoquercetin on biomarkers of endothelial and platelet activation, inflammation and ongoing blood coagulation.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- The names of the study drug involved in this study are/is: Isoquercetin
- Participants will receive study treatment for 1 year and will be followed for 30 days after the last dose.
- This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
- The U.S. Food and Drug Administration (FDA) has not approved isoquercetin as a treatment for any disease.
Study Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Eligible subjects require an established diagnosis of sickle cell disease/homozygous hemoglobin S (SCD-SS) or sickle cell disease hemoglobin β0-thalassemia (SCD-Sβ0-thal).
- Patients on other therapy including hydroxyurea will be included.
- Age 18-50 years.
Participants must have preserved organ and marrow function as defined below:
- leukocytes ≥2,000/mcL
- platelets ≥75,000/mcL
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- Estimated creatinine clearance ≥45 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Subjects with no evidence of worsening over the last 4 weeks (e.g. any acute complication of SCD including but not limited to VOC, acute chest syndrome and stroke, that required unscheduled medical attention or intervention) as determined by the investigator will be included.
- Patients on anticoagulation therapy will be excluded.
- The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of isoquercetin administration.
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Please ensure exclusion criteria are clearly worded to describe participants who will not be eligible.
- Participants may not be concurrently receiving any other study agents.
- Subjects with no evidence of worsening over the last 1 month (e.g. any acute complication of SCD including but not limited to VOC, acute chest syndrome and stroke, that required unscheduled medical attention or intervention) as determined by the investigator will be included.
- Familial bleeding diathesis.
- Known diagnosis of disseminated intravascular coagulation.
- Currently receiving anticoagulant therapy.
- Currently using daily use of aspirin (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to isoquercetin.
- Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness/social situations that would limit study compliance.
- Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin. These potential risks may also apply to other agents used in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ISOQUERCETIN
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits - ISOQUERCETIN: Oral Study Drug, 1 time per day, per predetermined dosed per 28 treatment cycle. This will continue for up to 337 days. |
Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in sP Selectin levels with isoquercetin
Time Frame: baseline to 28 Days
|
Comparisons between baseline and follow-up measurements (i.e.
change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses.
|
baseline to 28 Days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet dependent thrombin generation (coagulation)
Time Frame: baseline to 1 year
|
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
|
baseline to 1 year
|
sE-selectin (adhesion)-Biomarker
Time Frame: baseline to 1 year
|
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
|
baseline to 1 year
|
C-reactive protein CRP
Time Frame: baseline to 1 year
|
Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
|
baseline to 1 year
|
Number of Participants With Treatment-Related Adverse Events
Time Frame: start of study treatment up to 13 months
|
Sickle cell events such as SCPC, uncomplicated pain crisis, hospitalizations, emergency room visits, transfusions, acute chest syndrome and transfusion support will be summarized as annualized numbers.
Statistical comparisons will be made for each patient relative to the number from the previous year using a Wilcoxon rank-sum test.
|
start of study treatment up to 13 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20-087
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sickle Cell Disease
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Klein Buendel, Inc.National Institute on Minority Health and Health Disparities (NIMHD); Hilton...CompletedSickle Cell Disease | Sickle Cell Anemia in Children | Sickle Cell Thalassemia | Sickle Cell SC DiseaseUnited States
-
Nova Laboratories LimitedCompletedSickle Cell Disease | Sickle Cell Hemoglobin C | Sickle Cell-beta-thalassemia | Sickle-Cell; Hemoglobin Disease, ThalassemiaUnited Kingdom, Jamaica
-
SangartCompletedSickle Cell Disease | Anemia, Sickle Cell | Sickle Cell Anemia | Hemoglobin SC Disease | Sickle Cell Disorders | Sickle Cell Hemoglobin C DiseaseUnited Kingdom, France, Jamaica, Lebanon
-
SangartWithdrawnSickle Cell Disease | Anemia, Sickle Cell | Sickle Cell Anemia | Hemoglobin SC Disease | Sickle Cell Disorders | Sickle Cell Hemoglobin C DiseaseFrance, United Kingdom, Netherlands, Turkey, Bahrain, Belgium, Brazil, Lebanon, Qatar
-
University of British ColumbiaCompletedSickle Cell Disease | Beta-Thalassemia | Sickle Cell Trait | Sickle Cell-Beta Thalassemia | Sickle Cell-SS DiseaseCanada, Nepal
-
Sidney Kimmel Cancer Center at Thomas Jefferson...National Heart, Lung, and Blood Institute (NHLBI)TerminatedSickle Cell Anemia | Sickle Cell-hemoglobin C Disease | Sickle Cell-β0-thalassemiaUnited States
-
University of RegensburgRecruitingSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | HbS Disease | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SGermany, Austria
-
Centre Hospitalier Intercommunal CreteilRecruitingSickle-Cell Disease Nos With CrisisFrance
-
HemaQuest Pharmaceuticals Inc.TerminatedSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SUnited States, Lebanon, Egypt, Canada, Jamaica
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HemaQuest Pharmaceuticals Inc.CompletedSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SUnited States, Lebanon, Canada, Egypt, Jamaica
Clinical Trials on Isoquercetin
-
Nepal Health Research CouncilUnknown
-
Institut de Recherches Cliniques de MontrealPharmascience Inc.; SCiAN Services, Inc.; Quercis Pharma AGNot yet recruiting
-
Tulane UniversityNational Institute of General Medical Sciences (NIGMS)CompletedChronic Kidney DiseaseUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)Quercis Pharma AGCompletedSickle Cell DiseaseUnited States
-
Beth Israel Deaconess Medical CenterCompletedHealthyUnited States
-
University of ReadingBiotechnology and Biological Sciences Research Council; Quercegen PharmaceuticalsWithdrawnCardiovascular DiseaseUnited Kingdom
-
University of PennsylvaniaAbbottCompleted
-
Jeffrey Zwicker, MDNational Heart, Lung, and Blood Institute (NHLBI); Quercegen PharmaceuticalsCompletedThromboembolism of Vein VTE in Colorectal Cancer | Thromboembolism of Vein in Pancreatic Cancer | Thromboembolism of Vein in Non-small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonCompleted
-
AB ScienceRecruitingCOVID-19 | SARS-CoV 2 | Coronavirus Disease 2019France